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使用 SOMAscan 多重蛋白技术进行阿尔茨海默病生物标志物的发现。

Alzheimer's disease biomarker discovery using SOMAscan multiplexed protein technology.

机构信息

King's College London, Institute of Psychiatry, London, UK; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation Trust, London, UK.

SomaLogic, Boulder, CO, USA.

出版信息

Alzheimers Dement. 2014 Nov;10(6):724-34. doi: 10.1016/j.jalz.2013.09.016. Epub 2014 Apr 25.

DOI:10.1016/j.jalz.2013.09.016
PMID:24768341
Abstract

Blood proteins and their complexes have become the focus of a great deal of interest in the context of their potential as biomarkers of Alzheimer's disease (AD). We used a SOMAscan assay for quantifying 1001 proteins in blood samples from 331 AD, 211 controls, and 149 mild cognitive impaired (MCI) subjects. The strongest associations of protein levels with AD outcomes were prostate-specific antigen complexed to α1-antichymotrypsin (AD diagnosis), pancreatic prohormone (AD diagnosis, left entorhinal cortex atrophy, and left hippocampus atrophy), clusterin (rate of cognitive decline), and fetuin B (left entorhinal atrophy). Multivariate analysis found that a subset of 13 proteins predicted AD with an accuracy of area under the curve of 0.70. Our replication of previous findings provides further evidence that levels of these proteins in plasma are truly associated with AD. The newly identified proteins could be potential biomarkers and are worthy of further investigation.

摘要

血液蛋白及其复合物已成为阿尔茨海默病(AD)生物标志物潜在应用的研究热点。我们采用 SOMAscan 技术对 331 名 AD 患者、211 名对照者和 149 名轻度认知障碍(MCI)患者的血液样本中的 1001 种蛋白进行了定量分析。与 AD 结果相关性最强的蛋白水平是与α1-抗胰蛋白酶结合的前列腺特异性抗原(AD 诊断)、胰原激素(AD 诊断、左内嗅皮层萎缩和左海马体萎缩)、簇蛋白(认知下降速度)和胎球蛋白 B(左内嗅皮层萎缩)。多变量分析发现,有 13 种蛋白子集可准确预测 AD,曲线下面积为 0.70。我们对先前发现的进一步验证提供了更多证据,表明这些蛋白在血浆中的水平确实与 AD 相关。新鉴定的蛋白可能是潜在的生物标志物,值得进一步研究。

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